Pseudomonas keratitis is now perhaps the most important bacterial infection of the cornea. The infection is rapidly progressive and highly destructive. Little is known about the pathogenesis of the infection or the role of various host defense mechanisms. The results of chemotherapy are poor, and the value of chelating agents, enzyme inhibitors, immunization or corticosteroids is controversial. Physiologic concentrations of calcium have been shown to antagonize the antibacterial activity of the polymyxins and aminoglycosides (gentamicin) on Pseudomonas aeruginosa in vitro and in intraperitoneal infections of mice. Chelation of calcium enhances the activity of colistin in experimental mouse infections and may significantly increase the efficacy of polymyxins and aminoglycosides in treatment of Pseudomonas keratitis. Chelation may also inhibit the collagenases and reduce corneal injury. We have developed a reproducible, predictable model of experimental Pseudomonas keratitis in inbred guinea pigs. This model lends itself to precise quantitative studies. Using this model, we propose to examine the sequence of events in the pathogenesis of Pseudomonas keratitis, the role of Pseudomonas toxins, and the contribution of humoral and cellular factors in host defense. The optimal antibiotics and therapeutic regimen will be determined. The possible value of chelation, enzyme inhibitors, corticosteroids, immunization, and antiserum therapy will be evaluated. This study will provide a firm, experimental basis for the selection of optimal treatment of Pseudomonas keratitis in humans and will add to our understanding of the pathogenesis of Pseudomonas keratitis.